Project I: We propose a statistical chemical approach to provide firm experimental evidences for scrutinizing the biological significance of )- vs N-alkylation of the nucleic acid heterocycles in carcinogenisis. Thus, the O:N ratios and identity of the alkylation products of DNA and RNA will be determined by reacting them in vitro with known alkylating carcinogens. These O:N ratios can then be correlated with carcinogencity of these compounds. Conceivably, a weakly or noncarcinogenic alkylating agent may correlate with a lo set of O:N ratios, and conversely, a powerful carcingoen with high O:N ratios, or the reverse may prevail. Either pattern implicates the causal involvement of alkylation of nucleic acids in carcinogenesis. The third possibility of random correlations will tend to downgrade the direct interaction of the alkylating carcinogens with the nucleobasesas important in the induction of cancer. Project II: Our objective is to devise preventive measures against the pre- and ultimate carcinogens. Since most, if not all, chemical carcinogens, either are, or are converted in vivo to, reactive electrophilic derivatives such as cations and radical cations, it appears theoretically possible to ingest certain nontoxic antioxidant-nucleophilic agents to trap and detoxicate these electrophilic carcinoens. Considering that many common precarcinogens, viz. nitrosamines, arylamines, and polyaromtic hydrocarbons which are present in a normal dietary situation, are formed via the same types of reactive species, these antioxidant-nucleophilic agents may also work to reduce their formation. We suggest that the ascorbates (Vitamin C) and the tocopherols (Vitamin E) are excellent candidates in this function, and we propose to study their efficacy in these preventive actions.